title: Dysregulation of angiopoietin 1 and 2 in Escherichia coli O157:H7 infection and the hemolytic-uremic syndrome.
abstract: Escherichia coli O157:H7-associated hemolytic-uremic syndrome (HUS) is characterized by profound prothrombotic abnormalities. Endothelial dysfunction, manifested as dysregulation of angiopoietins 1 and 2 (Ang-1/2), could underlie HUS pathophysiology. We measured Ang-1/2 in 77 children with E. coli O157:H7 infection. Ang-1, Ang-2, and the Ang-2/Ang-1 ratio were significantly different in HUS vs the pre-HUS phase of illness or uncomplicated infection. Angiopoietin dysregulation preceded HUS and worsened as HUS developed. In vitro exposure of human microvascular endothelial cells to Shiga toxin recapitulated the in vivo observations. Angiopoietin regulation is profoundly affected before and during HUS, reflecting that subclinical endothelial dysfunction precedes overt microangiopathy.
authors.affiliation: Department of Medicine, Sandra A. Rotman, Laboratory for Global Health, Mount Sinai Hospital-University Health Network, University of Toronto, Ontario, Canada.
authors.forename: Andrea V
authors.initials: AV
authors.lastname: Page
authors.forename: Phillip I
authors.initials: PI
authors.lastname: Tarr
authors.forename: Sandra L
authors.initials: SL
authors.lastname: Watkins
authors.forename: Nimerta
authors.initials: N
authors.lastname: Rajwans
authors.forename: Tania N
authors.initials: TN
authors.lastname: Petruzziello-Pellegrini
authors.forename: Philip A
authors.initials: PA
authors.lastname: Marsden
authors.forename: Kevin C
authors.initials: KC
authors.lastname: Kain
authors.forename: W Conrad
authors.initials: WC
authors.lastname: Liles
mesh_terms: D042683:Angiopoietin-1 / Q000097:blood*; D042702:Angiopoietin-2 / Q000097:blood*; D002478:Cells, Cultured; D002648:Child; D042783:Endothelial Cells / Q000378:metabolism / Q000382:microbiology; D004927:Escherichia coli Infections / Q000097:blood*; D019453:Escherichia coli O157; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D006463:Hemolytic-Uremic Syndrome / Q000097:blood* / Q000382:microbiology; D006801:Humans; D011446:Prospective Studies; D022621:Shiga Toxin
chemical_list: D042683:Angiopoietin-1; D042702:Angiopoietin-2; D022621:Shiga Toxin
keywords: E. coli O157:H7; angiopoietin 1; angiopoietin 2; endothelial dysfunction; hemolytic-uremic syndrome